Proton Transfer in Bacterial Reaction Centers and Bacteriorhodopsin in the Presence of Dipyridamole

Abstract

Dipyridamole, 2,6-bis(diethanolamino)-4,8-dipiperidinopyrimido[5,4-d]pyrimidine (DIP), a well known vasodilator and inhibitor of membrane peroxidation has recently been shown a potential co-activator (modulator) in the MDR phenomenon in cancer therapy. It inhibits P-glycoprotein (Pgp) which is a efflux pump of anticancer drugs in tumor cells. For the first time it is shown that dipyridamole, markedly slows down the kinetics of the electrogenic phase of the photoelectric response in Rb. sphaeroides chromatophores which is due to the proton transfer from the external medium to the secondary quinone acceptor in the reaction center. In purple membranes from H. salinarium containing bacteriorhodopsin (bR) dipyridamole (in its charged state) significantly slows down the kinetics of the proton transfer to the Schiff base from the primary donor Asp-96 (in wild type bacteria) or from the surrounding (in D96N mutant). Dipyridamole is supposed to affect the proton-transfer via changes in structural dynamics of membrane proteins including modification of their system of hydrogen-bonds.